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Completed

NCT Number: NCT00002663

Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies

The purpose of this phase I/II trial is to study the side effects and best dose of biological therapy to treat patients at high-risk or with Epstein-Barr virus-associated lymphoma or lymphoproliferative disease.

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Key information

Conditions

EBV-induced Lymphomas Burkitt Lymphoma Chronic Disease DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes EBV-associated Malignancies Epstein-Barr Virus Infections Hematologic Diseases Hemic and Lymphatic Diseases Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, B-Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, T-Cell Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoproliferative Disorders Mycosis Fungoides Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Recurrence Sezary Syndrome Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma Tumor Virus Infections Virus Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Memorial Sloan Kettering Cancer Center

New York, 10065, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma, or other EBV-associated malignancy OR
  • Severely immunocompromised patients who develop blood levels of EBV DNA exceeding 500 copies/ml DNA, and are therefore at high risk for developing an EBV LPD

It is expected that five types of patients afflicted with EBV-associated lymphomas or lymphoproliferative diseases will be referred and will consent to participate in this trial. These are:

  • Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic marrow transplant.
  • Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant.
  • Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by HIV.
  • Patients who develop EBV lymphomas or lymphoproliferative diseases as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy.
  • Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and Non- Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma.

Exclusion criteria

The following patients will be excluded from this study:

  • Moribund patients who, by virtue of heart, kidney, liver, lung, or neurologic dysfunction not related to lymphoma, are unlikely to survive the 6-8 weeks required for in vitro generation and expansion of the EBV-specific T cells to be used for therapy and the subsequent 3 weeks required to achieve an initial assessment of the effects of infusions of EBV-specific T cells.
  • Pregnancy does not constitute a contraindication to infusions of EBV-specific T cells.

Treatment and study plan

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Biological

EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.

Other names: tabelecleucel (tab-cel®, ATA129), allogeneic EBV-CTLs, transplant donor-derived EBV-CTLs

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: From Day 1 through 251.1 months after Day 1 dose

    The ORR is defined as percentage of participants with best overall response of complete remission/response (CR) or partial remission/response (PR) based on investigator's assessment. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR is complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel; and PR is a 50 % or greater reduction in the size of all lymphomatous lesions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR is clearance of EBV without subsequent development of EBV+ LPD; and PR is at least a 10-fold decrease in EBV DNA levels.

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: From Day 1 through 251.1 months after Day 1 dose

    The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.

  2. OS Rate at 12 Months

    Time frame: From Day 1 through 12 months after Day 1 dose

    Percentage of participants with OS at 12 months are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.

  3. OS Follow-up Time

    Time frame: From Day 1 through 251.1 months after Day 1 dose

    The OS at follow-up time are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.

  4. Time to Response (TTR)

    Time frame: From Day 1 through 251.1 months after Day 1 dose

    The TTR was defined as the time from the date of the first dose of tabelecleucel or EBV-CTLs to the date of a PR or CR, whichever occurred first. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR was defined as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs; and a PR was defined as a 50 % or greater reduction in the size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR was defined as clearance of EBV without subsequent development of EBV+ LPD; and PR was defined as at least a 10-fold decrease in EBV DNA levels.

  5. Clinical Benefit Rate (CBR)

    Time frame: From Day 1 through 251.1 months after Day 1 dose

    The CBR was the proportion of participants who have achieved a CR, PR or SD assessed at least 28 days after first dose date of study drug. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBVCTLs; and a PR as a >= 50% reduction in size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR as clearance of EBV without subsequent development of EBV+ LPD; and PR as at least a 10-fold decrease in EBV DNA levels. The CBR was included specifically as clinically meaningful for solid tumor, namely LMS.

Sponsors and collaborators

Lead sponsor

Atara Biotherapeutics

Industry

Collaborators

  • Memorial Sloan Kettering Cancer Center
  • National Cancer Institute (NCI)

Registry information

Official study title

An Evaluation of the Toxicity and Therapeutic Effects of Epstein-Barr Virus-Immune T-Lymphocytes Derived From a Normal HLA-Compatible or Haplotype-Matched Donor in the Treatment of EBV-Associated Lymphoproliferative Diseases or Malignancies and Patients With Detectable Circulating Levels of EBV DNA Who Are at High Risk for EBV-Associated Lymphoproliferative Diseases

Important dates

Study start
1995
Primary completion
2019
Study completion
2019
First posted
Jan 27, 2003
Registry last updated
Feb 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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